The effect of blood-brain barrier (BBB) breakdown to proteins on the water content of brain tissue was studied in rabbits subjected to unilateral bolus injection of the animal's own blood into the internal carotid artery under pressure. The BBB was assessed with Evans Blue (EB) and with sodium fluorescein (NaF1) tracers. Also, the penetration of horseradish peroxidase (HRP) tracer, as well as the morphology of the brain tissue, was studied on the electron microscopic level. Water content of the brain tissue was evaluated with a modified specific gravity (SG) method. Quantitative evaluation of protein penetration into brain tissue was carried out using 125I labeled bovine serum albumin (BSA). Following closure of the barrier to proteins there was a progressive resolution of edema, in spite of the fact that the barrier remained open much longer for micromolecular substances, such as NaF1. Quantitative assayes revealed a direct relationship between amounts of extravasated BSA and water increments in the brain tissue. The results of this study indicate that breakdown of the BBB, allowing entry of serum proteins into extracellular spaces of brain parenchyma, free of any evidence of injury, is associated with significant increment in water content of this tissue, signifying development of vasogenic brain edema. This project is completed.